Nuclear osteopontin-c is a prognostic breast cancer marker

Zduniak, Krzysztof; Ziółkowski, Piotr; Ahlin, Cecilia; Agrawal, Anil Kumar; Agrawal, Siddarth; Blomqvist, Carl; Fjällskog, Marie-Louise; Weber, Georg F.

doi:10.1038/bjc.2014.664

Cited by 35 publications

(35 citation statements)

References 25 publications

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“…The reactivity of the autoantibodies was consistent with the appearance of splice variants in individual cancers. Breast cancer expresses OPN-a and -c, but not OPN-b (15,19,20). Liver cancer has elevated levels of OPN-a and -b, but not -c (14).…”

Section: Discussionmentioning

confidence: 99%

Anti‑osteopontin autoantibodies in various types of cancer

Alsarkhi

Weber

2018

Oncol Rep

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The aberrant processing of biomolecules by cancer cells may give rise to autoimmune phenomena. The metastasis gene osteopontin is alternatively spliced only in transformed cells, and the variants promote tumor progression. They may also serve as tumor-associated antigens, and their neutralization by autoantibodies could favorably affect prognosis. A competitive solid-phase ELISA format was applied to determine reactivity toward recombinant osteopontin in human serum or plasma samples. Approximately 35% of thyroid cancer patients and 15% of other cancer patients were found to harbor autoantibodies directed to osteopontin variants, averaging 21% of patients across all cancers studied. The reactivity of the autoantibodies was consistent with the differential appearance of splice variants in individual malignancies. In thyroid cancer, autoantibodies were found to be more frequently associated with a milder form of the disease. The junctions of osteopontin splice variants produced by cancers represent tumor-associated neo-epitopes. Whereas the uniqueness of their sequences renders the acquisition of tolerance during immune maturation improbable, their immunogenicity is predicted to be low. The rare occurrence of antibodies to either osteopontin-b or osteopontin-c suggests that the breaking of tolerance to full-length osteopontin is more prevalent in tumor autoimmunity than a reaction to a poorly immunogenic neo-epitope.

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Section: Discussionmentioning

confidence: 99%

Anti‑osteopontin autoantibodies in various types of cancer

Alsarkhi

Weber

2018

Oncol Rep

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“…After deparaffinization of sections with xylene, they were rehydrated in graded ethanol series (80%, 90%, 95%, and three 100%) and immersed in 0.3% hydrogen peroxide in methanol for 30 minutes at room temperature to block endogenous peroxidase activity. In the next step, for antigen retrieval, sections were incubated with retrieval solution ( [16], and the intensity score (IS) and proportional score (PS) were calculated and reported [17]. The IS was given as follows: 0= No positively stained cell or weak staining, 1= moderate staining, and 2=strong staining [17].…”

Section: Immunohistochemistrymentioning

confidence: 99%

Diagnostic and Biological Significance of Immunohistochemical Expression of Osteopontin and Ki67 in Fibro-osseous lesions of jaws

Sargolzaei

Ghelejkhani²,

Baghban

2017

J Islam Dent Assoc Iran

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Background and Aim: Fibrous dysplasia (FD) and ossifying fibroma (OF) are the most important fibro-osseous lesions (FOLs) of the jaws with similarities in radiographic and morphological features while showing completely different biological behavior. Limited studies have been evaluated immunohistochemistry markers, such as osteopontin (OPN) and osteocalcin to help differentiate these two lesions. This study aimed to assess the immunoexpression of OPN and Ki67 as potential markers for differentiation of different FOLs. Materials and Methods: This cross-sectional study was conducted on 12 FD, 19 OF, and eight FOL samples retrieved from the archives of the department of oral pathology. The specimens were examined immunohistochemically using streptavidin-biotin method for OPN and Ki67. The intensity score (IS), proportional score (PS) and total score (TS) were assessed in hard and soft tissue matrix and in mesenchymal cells for Ki67. The data were analyzed by independent samples Kruskal-Wallis. Results: Osteopontin showed positive immunoreaction in both stromal and trabecular components of all FDs and OFs. Among the scores, PS and TS of bone trabeculae were significantly different in FD and OF (P=0.005). Nevertheless, no significant difference was observed in Ki67 expression in mesenchymal cells (P=0.880) and OPN scores in soft tissue matrix between the lesions; their P-value were 0.336, 0.340 and 0.415 for IS, TS, and PS, respectively. Conclusion: Osteopontin can serve as a useful marker for differential diagnosis of FD and OF. However, we suggest evaluation of other NCMPs, especially functionally similar molecules such as bone sialoproteins (BSPs) in FOLs for differential diagnosis.

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“…In contrast, OPN-a promoted cell adhesion (64). A follow up study with increased number of patient samples found a more complex picture, but demonstrated strong association between nuclear OPN-c and mortality in patients with early onset breast cancer, while expression of OPN-a/b in the cytoplasm was associated with poor prognosis (68). In pancreatic cancer the picture is subtly different.…”

Section: Osteopontin Splice Variantsevidence For Association With Spementioning

confidence: 99%

Embracing the complexity of matricellular proteins: the functional and clinical significance of splice variation

Viloria

Hill

2016

Biomolecular Concepts

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Matricellular proteins influence wide-ranging fundamental cellular processes including cell adhesion, migration, growth and differentiation. They achieve this both through interactions with cell surface receptors and regulation of the matrix environment. Many matricellular proteins are also associated with diverse clinical disorders including cancer and diabetes. Alternative splicing is a precisely regulated process that can produce multiple isoforms with variable functions from a single gene. To date, the expression of alternate transcripts for the matricellular family has been reported for only a handful of genes. Here we analyse the evidence for alternative splicing across the matricellular family including the secreted protein acidic and rich in cysteine (SPARC), thrombospondin, tenascin and CCN families. We find that matricellular proteins have double the average number of splice variants per gene, and discuss the types of domain affected by splicing in matricellular proteins. We also review the clinical significance of alternative splicing for three specific matricellular proteins that have been relatively well characterised: osteopontin (OPN), tenascin-C (TNC) and periostin. Embracing the complexity of matricellular splice variants will be important for understanding the sometimes contradictory function of these powerful regulatory proteins, and for their effective clinical application as biomarkers and therapeutic targets.

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Nuclear osteopontin-c is a prognostic breast cancer marker

Cited by 35 publications

References 25 publications

Anti‑osteopontin autoantibodies in various types of cancer

Anti‑osteopontin autoantibodies in various types of cancer

Diagnostic and Biological Significance of Immunohistochemical Expression of Osteopontin and Ki67 in Fibro-osseous lesions of jaws

Embracing the complexity of matricellular proteins: the functional and clinical significance of splice variation

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